Table 2 Other MKIs for MAPK are being tested for different types of thyroid cancer but at the time of writing this article, none have reached phase III trials
From: Novel targeted therapies and immunotherapy for advanced thyroid cancers
Drug | Drug targets | Phase | Dosage | Patients | Partial response RR (%) | Progression-free survival PFS (months) | Adverse effects (%) | Drug discontinuation |
|---|---|---|---|---|---|---|---|---|
Multikinase inhibitors | ||||||||
Axitinib [130] | VEGFR, PDGFR, c-kit | II | starting dose of 5Â mg twice daily | 60 | 30 | 18.1 | Fatigue (50%), diarrhea (48%), nausea (33%), anorexia (30%), hypertension (28%), stomatitis (25%), weight loss (25%), and headache (22%) | 32 patients, 8 of them due to treatment side effects |
Motesanib [131] | VEGFR, PDGFR, c-kit | II | 125Â mg/day orally for up to 48Â weeks | 93 | 14 | 9.3 | Diarrhea (59%), hypertension (56%), fatigue (46%), and weight loss (40%) | 61 patients, 12 of them due to treatment side effects |
Sunitinib [132] | PDGFR, FLT3, c-kit, VEGFR, RET | II | 37.5Â mg/day orally | 35 | 31 | 12.8 | Neutropenia (34%), fatigue (11%), HFS (17%), diarrhea (17%), and leukopenia (31%) | 4 patients due to treatment side effects |
Pazopanib [133] | VEGFR, PDGFR, c-kit | II | 800Â mg/day orally in 4-week cycle | 37 | 49 | 11.7 | Fatigue (78%), skin and hair hypopigmentation (75%), diarrhea (73%), and nausea (73%) | 27 patients, 2 of them due to treatment side effects |
Dovitinib [134] | FGFR, and (VEGFR) | II | 500Â mg/day orally for five consecutive days, followed by a 2-day rest every week. | 40 | 20.5 | 5.4 | Diarrhea (54%), anorexia (36%), vomiting (26%), fatigue (23%), and nausea (21%) | 12 patients |
Imatinib [135] | BCR-ABL, PDGFR-α, PDGFR-β, c-fms, c-Kit, and RET | II | 600 mg/day orally | 15 | 0 | NR | Hypothyroidism (60%), rash, malaise, and laryngeal mucosal swelling (13%) | 10 patients, 3 of them due to treatment side effects |
Selumetinib (AZD6244) [43] | MEK-1/2 (one of MAPK), RAS, V600E BRAF | II | 100Â mg twice daily for 28-days cycles | 39 | 3 | 8 | Rash (77%), fatigue (49%), diarrhea (49%), and peripheral edema (36%) | Only 6 patients due to treatment side effects |
Selective BRAF inhibitors | ||||||||
Dabrafenib [136] | BRAF | I | 150 mg twice daily or 100 mg three times daily | 14 | 29 | 11.3 | skin papillomas (57%), hyperkeratosis (36%), alopecia (29%), elevated lipase (7%), grade 3 elevated amylase (7%), grade 3 fatigue (7%), grade 3 febrile neutropenia (7%), and grade 3 cutaneous squamous cell carcinoma (7%) | None |
Vemurafenib [137] | BRAF | II | 960 mg orally twice daily | 51 | 35 | 15.6 | squamous cell carcinoma of the skin (23.5%), lymphopenia (8%), and increased γ-glutamyl-transferase (8%) |  |